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Some rare mutations linked to autism may boost a person’s chances of having the condition less than prior work suggests, according to a new study, but they can also raise the likelihood of having other conditions.

Repeated or missing stretches of DNA, or copy number variations (CNVs), increase the chances of having any of multiple neurodevelopmental or psychiatric conditions, including autism. Previous studies, however, focused on people with clinical diagnoses. Because many people might carry a CNV without any obvious effects, it was unclear how much CNVs increased the chances of having a neuropsychiatric condition overall.

Now scientists have conducted what may be the first population-wide review of the prevalence and impact of CNVs in six chromosomal regions linked to a range of neurodevelopmental and psychiatric conditions: 1q21.1, 15q11.2, 15q13.3, 16p11.2, 17p12 and 17q12. They also looked for links between the CNVs and other conditions, such as epilepsy and fertility, and mortality.

Having a CNV in any of the regions except 17p12 significantly increased the likelihood of autism and most other diagnoses considered, including attention deficit hyperactivity disorder (ADHD), schizophrenia, major depressive disorder and intellectual disability, the results showed. And deletions in 1q21.1 substantially increased the risk of bipolar disorder in men and major depressive disorder in both sexes. CNVs were tied to physical ailments as well — a deletion in 15q13.3, for example, was linked to inflammation of the thyroid gland.

“We now have a realistic sense of which disorders can be expected and the likelihood that a given person develops a given illness,” says lead investigator Thomas Werge, professor of clinical medicine at the University of Copenhagen in Denmark.

The results indicate that autistic people are more likely to carry CNVs than non-autistic people and stand to benefit from newborn screening, says Marianne van den Bree, professor of psychological medicine and clinical neurosciences at Cardiff University in Wales, who did not take part in this research.

“Ideally, the families of babies born with a copy number variant linked with high risk of a neuropsychiatric disorder should be offered the opportunity of continuous monitoring and early implementation of support,” she says.

Werge and his colleagues analyzed genetic and health care data from 87,377 people born in Denmark between 1 May 1981 and 31 December 2005 who were included in the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) database. The sample — roughly 2 percent of the Danish population born during the period studied — included 57,377 people clinically diagnosed with ADHD, major depressive disorder, schizophrenia, autism or bipolar disorder, along with 30,000 people drawn at random from the database.

Two of the CNVs — deletions in 1q21.1 and 17q12 — boosted the likelihood of autism more than others, the team found. CNVs in 1q21.1, 15q13.3, 16p11.2 and 17q12 also increased the chances of having autism and co-occurring intellectual disability or ADHD — and, to a lesser extent, CNVs in 15q11.2 and 17p12 did as well. The scientists detailed their results in November in JAMA Psychiatry.

Overall, the CNV-linked increases in risk were generally lower than previous estimates, which van den Bree says are likely upper estimates because they are based on analyses of clinically diagnosed groups.

Duplications in 16p11.2 increased the chances of autism in men, and deletions in this stretch increased the chances of autism in women. The risks that many CNVs pose to an individual may depend on sex, Werge says, which could explain a range of sex differences seen in psychiatric conditions.

Deletions in 17p12 lowered the likelihood of many of the psychiatric diagnoses, the researchers found. This discovery warrants follow up, they say, because if confirmed it could point toward new therapeutic opportunities.

Because this study followed people only until age 32, it does not provide insights into later-onset disorders, Werge cautions. And because the researchers relied on hospital records, they could not track clinical outcomes. They plan to follow socioeconomic status and non-hospital medical data, such as general-practitioner-prescribed medications in people with CNVs, in their next studies, Werge says. They also plan to study more CNVs, along with single-letter DNA variations.

Future research “should investigate the impact of these rare variants on early development,” says Samuel Chawner, a research fellow in psychology at Cardiff University, who did not participate in this study. “However, this approach would require large-scale studies that conduct detailed developmental assessments that go beyond information available in medical records.”

Scientists also need to study the implications of carrying CNVs in people of non-European ancestry, van den Bree says. “Most genetics research to date has been based on participants of European ancestry. It is poorly understood whether carrying a copy number variant has similar consequences in people of different ethnic backgrounds. Insights into this matter would allow better tailored care for patients and their families.”

Cite this article: https://doi.org/10.53053/NPAH2204

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Millions of infants have benefited from Don Bailey’s work as a member of the U.S. Advisory Committee on Heritable Disorders in Newborns and Children. For six years, he helped decide which conditions doctors should screen for in all babies born in the United States.

The program is one of the country’s greatest public-health successes, says Bailey, now a distinguished fellow at the Genomics, Bioinformatics and Translational Research Center at the nonprofit RTI International in Research Triangle Park, North Carolina. But, he warns, the process of adding new conditions to the program happens too slowly to keep pace with an anticipated influx of cell- and gene-based therapies — at least 60 in the next decade, by some projections. Several of these therapies target autism-linked genetic conditions, including Angelman syndrome, Rett syndrome and fragile X syndrome.

“The system is going to be under tremendous pressure to make changes that it simply can’t make right now under the current structure,” Bailey says. “And so something needs to be done so that the next 60 years are as successful as the last 60 years.”

To start getting the system up to speed, in December 2020, Bailey and his colleagues convened 42 experts on newborn screening — including researchers, clinicians and representatives from patient advocacy groups, state agencies and pharmaceutical companies — to brainstorm upgrades. In a new report, the group expressed little confidence that the current system could approve even 30 conditions by 2030 and generated 20 possible solutions to boost it, including establishing regional screening labs and building a national program for identifying genetic variants.

Spectrum talked to Bailey about how the experts came together and the complex questions they considered.

Spectrum: What was your motivation for convening this group of experts?

Don Bailey: When I served on the secretary’s advisory committee, parents would come and talk about their child’s condition, and they were really wondering why newborn screening did not include it. But often there was a lot of missing data that the committee needed, and parents ended up being frustrated about the slow review process. [To be added to the list of recommended conditions for screening, a condition must have a reliable test and a treatment shown to improve outcomes if given early in life.] The advent of gene therapy and gene editing will open the possibility of an even more impactful newborn screening system, but it also really heightened the intensity.

There is a pipeline of at least 60 to 100 therapeutic products that are being developed for single-gene and rare disorders. How can newborn screening be prepared for the possibility of many more conditions that could benefit from early identification? In fact, when I left the committee, my departing words were, “This is a great group, but there’s no way we can sustain this model of reviewing one disorder at a time and taking two to three years to do it.”

S: Why did you want to solicit so many different perspectives?

DB: The system is so complex and intertwined that the solutions have to be integrated across different stakeholder groups. Sometimes we don’t engage parents as much as we should in these decisions. Sometimes it can be almost adversarial. You have parents pushing on one side, saying, “Let’s work faster to get my family’s condition on newborn screening now. There is no reason for this not happening.” But then you have your state or federal officials saying, “Wait a minute, we need to take some time to do due diligence. And we have all these other priorities too.” We wanted to model what we hoped would be a true interaction, and we wanted everyone there to be equals. That has to be what happens in the future.

S: Could early diagnosis and intervention, which are key priorities for autism researchers, factor into newborn screening in a reimagined system?

DB: To approve a condition, the committee needs to see a benefit to screening all newborns. Right now, the notion of ‘benefit’ is pretty narrowly defined as access to a drug, surgery, dietary change or something ‘medical’ or ‘biological’ that has been proven to make a change directly in children’s lives. Such treatments are not currently available if an infant could be screened for autism. One suggestion from the survey is to expand the concept of benefit to include things like access to early intervention or shortening the diagnostic odyssey. For some families, it would provide information about future children. All of those are additional potential benefits, but they’re not factored into the decision-making process right now.

State officials are concerned — I think legitimately — that if we opened the door to all those other concerns, then really nothing would be excluded. In their minds, and I think rightfully so, it dilutes the evidence-based process. And they’re concerned about their ability to actually implement so many conditions at once, because they have to validate the screening, set up follow-up systems, do lots of testing ahead of time to set cutoff levels, and so forth.

Parents, on the other hand, view those as really important outcomes. They are always asking, “Why aren’t you considering information or access to early-intervention programs as key considerations for doing newborn screening?”

S: Could changes in newborn screening affect how autism researchers study early intervention?

DB: It is highly unlikely that autism will be a part of newborn screening in the near future. The implicit promise of newborn screening is that we will find almost every child who has this condition. Maybe someday somebody we will invent a brain scan or find a biomarker that can identify autism at birth. But I’m going to guess that there will not be one magic bullet there.

A genetic condition that is associated with autism, on the other hand, could get added to the list. The question is always, “Do we know if early treatment is going to be effective for children with this particular disorder?” We’ve got thousands of rare conditions, and you can’t do thousands of studies on the effectiveness of early treatments for each one of them. For almost every autism-associated condition, we’d like to know: If you identified this baby with fragile X or Angelman syndrome or Prader-Willi syndrome or Rett syndrome at birth and started an early treatment program, how much could you change developmental trajectories? How much could you reduce the secondary complications? How much could you reduce the prevalence of autism or the magnitude of autism traits in those children?

It is almost impossible to answer those questions if you cannot identify the babies in the first place. So you have a ‘Catch-22’ situation: You cannot prove the benefits of early detection without screening, but you cannot do screening without some evidence of the benefits of early detection. I think the autism community is better off trying to lower the age of developmental screening and other kinds of assessments that are more proven now.

S: Could polygenic risk scores be considered?

DB: There’s a whole move now toward polygenic risk scores. This is an effort to pull together a lot of different genes and then create an algorithm that predicts future disease state. There is an exploding literature on polygenic risk scores. However, so far, they’re woefully inadequate for newborn screening. We will never use polygenic risk scores until they’re a lot more accurate. I’m confident that sometime — maybe not in our lifetime — there will be valid polygenic risk scores that actually could do a pretty good job of detecting these very complex conditions, such as schizophrenia, but there’s so much work to be done before that can happen. And autism is a clear example of that.

S: What did you take away from this project, and what are the next steps?

DB: I was pretty confident that some kind of change needed to be made, but I was really surprised at the strength with which the study participants endorsed that statement. People with all these different perspectives said, “We are not ready as a system today to make these kinds of changes.” That creates a heightened sense of urgency.

We focused on individual solutions, but what’s going to have to happen next is to figure out which solutions need to be implemented together. I came away with optimism that we had for the first time done an inventory of solutions rather than just raising the problems. I feel good about that, and I think it will advance the field. But there’s so much work to be done. It’s only the first step.

Cite this article: https://doi.org/10.53053/LRNS7670

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Loss of the autism-linked gene ASH1L leads to excess synapses and autism-like behaviors in mice, according to a study published today in Neuron. Boosting the activity of another gene that is downregulated in the mice as a result of the loss of ASH1L reverses some of those changes, the researchers also found.

Some research suggests that autistic people have altered synaptic pruning — the brain’s process of editing unnecessary neuronal connections in early childhood. The fact that targeting an ASH1L-regulated gene restored this process provides a “promising and more specific therapeutic approach” for autistic people with ASH1L mutations, says Jin He, assistant professor of biochemistry at Michigan State University in East Lansing, who was not involved in the study.

The new work, led by Ji-Song Guan, associate professor of neuroscience at ShanghaiTech University in China, is also the first to show that loss of just one copy of ASH1L can cause autism-like traits in mice, He adds. Last year, He and his colleagues created the first ASH1L knockout mice missing both copies of the gene in their brains. But the new mice, missing just one copy, more closely model what happens in autistic people who have ASH1L mutations, He says. Guan did not respond to requests for comment.

The ASH1L mice appear to have trouble differentiating between sounds, a challenge sometimes seen in people with autism. Connecting an autism gene with synapse formation and auditory challenges is exciting, says Sofia Lizarraga, assistant professor of neurobiology at the University of South Carolina in Columbia, who was not involved in the work.

“It was very elegantly done,” Lizarraga says. “Looking at that connection with the auditory discrimination and synapse elimination is actually pretty novel.”

Guan and his colleagues ran the ASH1L mice through a battery of behavioral tests. Unlike control mice, the ASH1L mice did not spend more time with an unfamiliar mouse than a new one, suggesting a difference in social behavior. By comparison, they also made fewer vocalizations to their mothers as pups, showed more anxiety and spent more time burying marbles, an activity considered akin to repetitive behaviors in people with autism.

When the team trained the mice to lick a waterspout after hearing a specific tone, the ASH1L mice learned the task as well as control mice. But new tones more frequently prompted them to lick than control mice, suggesting they have difficulty discriminating between sounds.

Cortical neurons from ASH1L mice cultivated in a dish had more branching arms, called dendrites, than those from control mice. They also eliminated fewer connections than the neurons of controls did after the researchers activated the cells.

Similarly, ASH1L mice had fewer pruned synapses than controls did after learning to associate a specific sound with a mild electric shock. The findings suggest that ASH1L helps regulate activity-dependent synaptic pruning, which would explain the abundance of synapses in mice missing a copy of ASH1L, the investigators write in the paper.

Hundreds of genes showed altered expression in the ASH1L mice at both 1 month and 1 year of age. Many of the genes are involved in synapse development in the auditory cortex and dorsal striatum, a brain region that facilitates movement. One gene in particular, EPHA7, had low expression levels in both areas at both ages.

Stimulating EPHA7 using a molecule that binds to it in ASH1L neurons increased the cells’ synaptic pruning. ASH1L mice trained on the water-lick task performed as well as control mice after receiving an injection of the treatment to the auditory cortex.

The findings identify new molecular and cellular mechanisms that might underlie some autism traits, He says, although it’s unlikely that all of them are tied to EPHA7. Future work should examine how other genes regulated by ASH1L contribute to autism, he says.

The team could also investigate what happens when ASH1L is knocked out in cells other than neurons, such as microglia, Lizarraga says.

The post Loss of autism-linked gene alters synapse development in mice appeared first on Spectrum | Autism Research News.

The investigational drug trofinetide, an analogue of insulin-like growth factor 1 (IGF-1), helps ease issues such as anxiety and breathing problems in girls and young women with Rett syndrome, according to unpublished results from a placebo-controlled trial.

Rett syndrome is caused by mutations to MECP2, a gene found on the X chromosome. The condition affects mostly girls and is characterized by motor issues, breathing and eating problems, anxiety and autism. There are no drugs approved to treat it.

Injections of IGF-1, a protein produced in the liver, repair malfunctioning synapses in mice missing MECP2, according to past research. These mice showed improved breathing and heart function, but not motor skills or coordination. Trofinetide mimics only a portion of IGF-1, and it has been modified to last longer in the body and be administered orally.

In the new trial, 187 girls and young women with Rett syndrome, ranging from 5 to 20 years of age, took twice-daily doses of a liquid containing trofinetide or a placebo for 12 weeks. The 91 participants who took trofinetide showed significantly more improvements in Rett syndrome traits than those on placebo, according to caregiver and physician ratings.

Acadia Pharmaceuticals, the company that sponsored the trial, announced the results in a press release in December. Based on the trial results, Acadia plans to submit a new drug application for trofinetide to the U.S. Food and Drug Administration by the middle of 2022, says Deb Kazenelson Deane, senior director of product communications at Acadia.

The magnitude of improvement was small, raising questions about whether the drug’s effects are clinically meaningful. But given the dearth of treatments for Rett syndrome, any improvement is important, says Sébastien Jacquemont, associate professor of pediatrics at the University of Montreal in Canada, who was not involved in the study.

“There has been such a small amount of trials that have shown a clear, significant effect, that at this point, as a researcher and as a clinician, I don’t really care if it’s significant clinically,” Jacquemont says. The statistically significant results indicate that researchers have identified a valid treatment target, he says.

The study participants were randomly assigned to the treatment and placebo groups, and the trial was double-blind, so neither the families nor the researchers knew to which group any participant belonged. Parents or caregivers reported their child’s progress over the course of the trial using the Rett Syndrome Behavior Questionnaire (RSBQ), which asks about common Rett traits. Clinicians rated the severity of participants’ traits on the Clinical Global Impressions Scale.

On both measures, participants who took trofinetide showed more improvement than the placebo group, according to a December presentation by Acadia in an investor webcast. The RSBQ may not be a reliable outcome measure for clinical trials, according to a 2020 analysis, but the addition of a clinician-reported scale supports the validity of the RSBQ findings, Deane says.

What remains to be seen is exactly how clinically meaningful these improvements are, says co-principal investigator Elizabeth Berry-Kravis, professor of pediatrics and neurological sciences at Rush University Medical Center in Chicago, Illinois.

“There are those in the rare disease field, and many families, who would tell you that anything that’s an improvement is a clinically meaningful improvement because we have nothing that’s specifically targeted to our disease,” she says.

Because the Food and Drug Administration is increasingly stringent about ensuring that clinical trials yield results that are not only statistically significant but also clinically meaningful, it’s possible that Acadia’s discussions with the regulator will result in requirements to that end, Berry-Kravis says.

But future Rett therapies will probably include some combination of drugs or other therapies, Jacquemont says. “I don’t think any treatment alone would have an effect of clinical significance.”

Cite this article: https://doi.org/10.53053/BMOS2862

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The authors of a 2013 study that appeared to uncover a mechanism by which the immune system influences synapse development have retracted the paper after discovering errors and failing to replicate their findings.

The study, published in Nature Neuroscience, showed how astrocytes secrete an immune protein called transforming growth factor-beta (TGF-beta) that kicks off a ‘complement cascade’ process, prompting microglia to prune weak synapses in the visual system of juvenile mice. Some researchers have suggested that this pruning process may falter in the brains of people with autism.

The article has been cited more than 350 times, according to Clarivate’s Web of Science.

The retraction negates only the identification of TGF-beta as a regulator of the cascade, says Beth Stevens, associate professor of neurology at Harvard University and the study’s lead investigator. It does not undermine researchers’ understanding of how the immune system and microglia are involved in synapse development.

“The foundational work on complement and pruning, the role of microglia and pruning, the potential relevance to development — none of that really has been impacted by this one singular study,” Stevens says.

Stevens says she is not aware of other papers that have examined TGF-beta’s role in synaptic pruning.

Her lab members brought to her attention issues with some of the paper’s underlying data, according to a statement Stevens posted on her lab website.

At the time, she and her colleagues alerted the journal editors and repeated some of the study’s main experiments, Stevens says, which required reviving mouse lines that had been retired. Some of the findings weren’t as “solid” in the replicated work, she says, and the team was not able to redo other parts of the work that were in question years after the fact, leading to Stevens’ decision to retract the work.

“No one wants to have to correct scientific work,” Stevens says. “The most important thing that we did and that I am proud of is that we saw it, we dug into it deeply.”

Stevens “should be commended for detecting and double-checking the errors and for her courage in calling for a retraction,” Cornelius Gross, interim head of the European Molecular Biology Laboratory in Monterotondo, Italy, wrote in an email to Spectrum. Gross’ lab has researched how microglia act on synapses.

When the paper came out, “it pushed people to think also about the role of astrocytes in synaptic pruning,” Gross says.

A commentary published along with the original study noted that it was the first to link three types of brain cells — astrocytes, neurons and microglia — and marked a “critical” finding that “lays the foundation for future studies aiming to further identify the mechanisms of multicellular and even multisystemic neural-glial-immune interactions in brain development and health.” The commentary’s authors have also retracted that work, as it relied on the paper’s now-questioned data for its conclusions, according to the retraction notice.

In June and July 2020, anonymous comments on the post-publication review site PubPeer pointed out multiple inconsistencies in the study’s data, including duplicated values in data tables, discrepancies between figures and source data, and at least one duplicated figure. (PubPeer commenters can choose to remain anonymous.)

Stevens says she was already aware of the issues and in touch with the journal at the time the comments were posted. She replied to the comments to that effect the same month.

“Any retraction is unfortunate, but it appears that Dr. Stevens acted properly by drawing the matter to the attention of the journal as soon as the issues became apparent,” Paul Morgan, professor of complement biology at Cardiff University in Wales, wrote in an email to Spectrum. Morgan cited the paper in a 2021 study but said the retraction does not affect the statements in his work that relied on Stevens’ paper, as other researchers have confirmed them.

This retraction is the second for Stevens’ co-investigator on the 2013 study, Allison Bialas, who was a graduate student in Stevens’ lab. In 2020, Nature retracted a 2017 study about research Bialas had worked on as a postdoctoral researcher at Harvard. That paper also examined immune system effects on microglia and synapse development.

In December 2021, Bialas, Stevens and their colleagues issued corrections to another paper, this one from 2016, on the immune system and schizophrenia, citing errors in descriptions of the experiment that did not affect their results or conclusions. Among the errors was the inclusion of an image of brain tissue from a wildtype mouse that had first appeared in the now-retracted 2013 study.

Bialas did not respond to Spectrum’s request for comment. Bialas’ current affiliation is unclear; a Harvard spokesperson confirmed she completed her postdoctoral appointment at Harvard in July 2020. Her most recent work, published in 2020, states that she is employed by the French pharmaceutical company Sanofi.

Cite this article: https://doi.org/10.53053/YFRZ6893

The post Researchers retract study of an immune effect on synapse development appeared first on Spectrum | Autism Research News.

Ready for your weekly recap of autism research tweets?

First up in this edition of Spectrum’s Community Newsletter, the cover of The Lancet on 15 January featured a quote from the journal’s recent commission on the future of autism care and clinical research.

On this week’s cover, a quote from The Lancet Commission on the future of care & clinical research in #autism: https://t.co/4GotrTcBmO

Access the new issue: https://t.co/VSFYpk0XVt pic.twitter.com/XKwsUIZLJf

— The Lancet (@TheLancet) January 14, 2022

The issue offers a report from the commission, plus a profile of commission co-chair Catherine Lord, distinguished professor of psychiatry and education at the University of California, Los Angeles, and a comment from Monica Juneja, professor of pediatrics at Maulana Azad Medical College in New Delhi, India, and her colleagues. All are useful reads before tuning in to the Spectrum webinar this coming Wednesday, 26 January 2022, at 11 a.m. EST with Lord and her commission co-chair, Tony Charman, chair of clinical child psychology at King’s College London in the United Kingdom.

Also on Wednesday at 11 a.m. EST, Jill Silverman, associate professor of psychiatry and behavioral sciences at the University of California, Davis, will talk about translational biomarkers, tweeted Silvia De Rubeis, assistant professor of psychiatry at the Seaver Autism Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai in New York City, who coordinates the center’s seminar series. Both talks will be recorded, so you can watch one or the other later.

Next on our ????2022????lineup is @jill_silverman_ (@ucdavis)

Join us on @worldwideneuro on Wed 26th to learn about translational biomarkers of preclinical models of neurodev disorders ????@worldwideneuro https://t.co/efdzvIE0bf @SeaverAutism @SinaiBrain @MountSinaiPsych https://t.co/PmTCL8oSg0 pic.twitter.com/jpudJAShGV

— Silvia De Rubeis (@DeRubeisLab) January 13, 2022

The International Society for Autism Research (INSAR) has launched a new initiative, the INSAR Community Collaborator Request, to connect autism researchers with autistic adults, among other stakeholders, to pursue participatory research, autistic researcher Zack Williams tweeted. Williams, an M.D./Ph.D. student at Vanderbilt University in Nashville, Tennessee, gives details in a thoughtful thread, with links to additional resources from Sue Fletcher-Watson, professor of developmental psychology at the University of Edinburgh in Scotland.

????New exciting opportunity for both autistic people and autism researchers???? The @AutismINSAR Community Collaborator Request (#ICCR) is a new initiative that helps connect autism researchers and autistic adults (or other stakeholders) to collaborate on participatory research 1/???? https://t.co/v9laGNuyXS

— Zack Williams (@QuantPsychiatry) January 20, 2022

Nature Medicine starred a research paper published in November in Cell that flips the link between autism and microbiome differences: Instead of causing the condition’s traits, microbiome differences may result from the dietary preferences many autistic people have. Spectrum covered some of the work in October.

Research Highlight: #microbiome alterations have been associated with #autism, but a study published in @CellCellPress suggests that this may be a consequence of autism-related dietary preferences, rather than a causal factor.https://t.co/fbPRWFqQBb

— Nature Medicine (@NatureMedicine) January 20, 2022

And, “The emperor has no clothes,” tweeted Andrew Whitehouse, professor of autism research at Telethon Kids and University of Western Australia in Perth, about a new test for autism that was granted ‘breakthrough device’ status by the U.S. Food and Drug Administration in December. Spectrum covered the agency’s announcement last week.

No clinical validity at all for how hair analysis can diagnose a complex, neurodevelopmental and behaviourally-defined condition.
The emperor has no clothes.

FDA cites hair-based autism diagnostic aid as ‘breakthrough’ https://t.co/QdvvXg5j4S Newsletters via @Spectrum

— Andrew Whitehouse (@AJOWhitehouse) January 17, 2022

That’s it for this week’s Community Newsletter! If you have any suggestions for interesting social posts you saw in the autism research sphere, feel free to send an email to news@spectrumnews.org.

Cite this article: https://doi.org/10.53053/PPLU3820

The post Community Newsletter: Upcoming webinars, participatory research resources, research reactions appeared first on Spectrum | Autism Research News.

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One paper is about the aesthetic beauty of plant landscapes. Another reviews the use of anesthetic drugs in cancer patients. A third aims to optimize how efficiently buses operate using deep learning.

Yet they each cite studies on autism — including one in the International Journal of Environmental Research and Public Health and one in Neural Computing and Applications. And no one is quite sure why.

Autism studies, among others, are appearing in the reference lists of entirely unrelated papers, suggesting what a few scholars worry is a larger plot to manipulate citations and artificially inflate the impact of research papers.

Both of the autism papers were co-authored by N. Arunkumar, assistant professor of biomedical engineering at ​​Rathinam Technical Campus in Tamil Nadu, India. Arunkumar also co-authored the study on anesthetic drugs that cites one of his autism papers.

Several posts on PubPeer — an online platform that researchers use to discuss journal publications — point out that in many cases Arunkumar’s studies, including those on autism, are being cited completely out of context.

Guillaume Cabanac, associate professor of computer science at the University of Toulouse in France, told Spectrum that PubPeer entries about papers containing nonsensical references represent a growing trend.

“These papers cite a paper on autism, but there is no relation between the citing paper and the cited reference,” Cabanac says. From these citation patterns, one may conclude that autism is a hot research topic, as studies in the field are being cited from several other disciplines, he says. “But it’s not really the case,” Cabanac adds. “It’s more likely a scam.”

Multiple studies that cite Arunkumar’s papers have been retracted, withdrawn or earned expressions of concern, although none of his own papers have been retracted, according to the Retraction Watch Database. (A co-founder of Retraction Watch, Ivan Oransky, is also editor-in-chief of Spectrum.)

Out of the 91 studies listed on Arunkumar’s Google Scholar page, only 4 have “autism” in their titles. His publication list suggests that he has authored studies on a variety of topics, including lung cancer, Parkinson’s disease and artificial intelligence.

Still, the firm Clarivate Analytics included Arunkumar on its list of the world’s top 1 percent of cited scientists in his field, following a sudden spike in citations of his papers in 2018. In that year, Arunkumar racked up nearly 800 citations — significantly more than in the previous seven years of his career combined.

Arunkumar is not the only researcher with a curious citation record. His frequent co-author Mohamed Elhoseny, associate professor of information systems at the University of Sharjah in the United Arab Emirates, is also listed as a highly cited researcher by Clarivate. Between 2018 and 2021, Elhoseny authored between 40 and 60 papers per year while also peer-reviewing hundreds of others: In 2018 alone, he reviewed more than 300 manuscripts.

Commenters on PubPeer noted, however, that Elhoseny’s studies — none of which appear to concern autism — had been cited in 144 papers published by the Journal of Intelligent and Fuzzy Systems (JIFS). Nearly all of those papers were part of special issues that were often edited by guest editors, and at least two were co-edited by Elhoseny himself.

Spectrum has contacted Arunkumar and Elhoseny twice by email for comments but has yet to hear back.

In November 2021, IOS Press, which publishes JIFS, retracted 49 papers after finding that “these articles cite literature sources that have no relation to the subject matter of the citing article.” The retraction notice concluded: “This could be the result of a deliberate attempt to engineer the citation performance of the scientific literature.” Last year, Clarivate delisted JIFS from its journal citation reports for allegedly stacking citations.

In September 2021, publishing giant Springer Nature flagged 436 studies — including the study about plant aesthetics — published as part of special collections in its journals with ‘expressions of concern’ amid worries that rogue editors or impersonators may have deliberately manipulated the process.

“Sometimes you will get situations where the guest editors of special issues may use that special issue as a vehicle to promote themselves, journals they are associated with, and their own colleagues,” says Matt Hodgkinson, head of research integrity at the open-access publisher Hindawi in London, England.

A spokesperson for Clarivate declined to comment on individual researchers but pointed Spectrum to the methodology the firm uses to determine highly cited researchers, noting that in 2019 the firm started excluding authors who cite their own work excessively. The methodology reads: “Researchers found to have committed scientific misconduct in formal proceedings conducted by a researcher’s institution, a government agency, a funder or a publisher are excluded from our list.”

Cyril Labbé, a computer scientist at the Université Grenoble Alpes in France, disagrees with judging researchers on the basis of their citations. “To me, these [kinds] of ‘mechanic’ and ‘blind’ [rankings] are completely disconnected from what counts in science,” he says. It “doesn’t reflect the whys of the citations and so should not be used as a proxy for detecting people who are valuable to science.”

Hodgkinson says that this may be a case of coercive citations, a practice in which journal editors or peer reviewers demand that study authors add certain citations as a prerequisite for having their papers accepted and published.

Cabanac says it’s important that publishers investigate to keep their journal papers free of unnecessary citations and to find out whether authors are accomplices in this practice. “I can imagine two explanations [for] these odd citations,” Labbé adds. “One being insertion of random out-of-context citations in random texts. The other one is intentional citation manipulation. The latter seems to be more probable.”

Cite this article: https://doi.org/10.53053/MGSA7457

The post Why was a study about autism cited by a paper on plant beauty? appeared first on Spectrum | Autism Research News.

Autism is thought to arise during prenatal development, when the brain is spinning its web of excitatory and inhibitory neurons, the main signal-generating cell types in the cerebral cortex. Though this wiring process remains mysterious, one thing seemed certain after two decades of studies in mice: Although both neuron types arise from radial glia, excitatory neurons crop up in the developing cortex, whereas inhibitory neurons, also known as interneurons, originate outside of the cortex and then later migrate into it.

Not so in the human brain, according to a study published in December in Nature. A team of researchers led by Tomasz Nowakowski, assistant professor of anatomy at the University of California, San Francisco, used a new viral barcoding method to trace the descendants of radial glial cells from the developing human cortex and found that these progenitor cells can give rise to both excitatory neurons and interneurons.

“This is really a paradigm-shifting finding,” Nowakowski says. “It sets up a new framework for studying, understanding and interpreting experimental models of autism mutations.”

Nowakowski spoke with Spectrum about the discovery’s implications for studying the origins of autism in the developing brain.

Spectrum: Why did you investigate this topic?

Tomasz Nowakowski: My lab and I are interested in understanding the early neurodevelopmental events that give rise to the incredible complexity of the human cerebral cortex. We know especially little about the early stages of human development, primarily because a lot of our knowledge comes from mouse models. As we’ve begun to realize over the past decade, the processes that underlie development of the brain in humans and mice can be quite different.

The key motivation comes from the findings that many psychiatric neurodevelopmental conditions, including autism, manifest very early in life and are theorized to be a consequence of disruptions occurring in these early stages of brain development.

S: How did you react when your result differed so dramatically from what was previously thought?

TN: The funny story behind this is that I didn’t want to believe our results and resisted for a long time. The hypothesis that cortical radial glia generate cortical interneurons locally in primates, but not in mice, was proposed almost 20 years ago, but it has been very controversial and not generally accepted. As a scientist, I see my role as being the greatest skeptic of my own work, particularly if the findings have such long-standing implications. Therefore, the credit really goes to the trainees in my lab who pushed back and produced the evidence in support of this model.

S: What implications does your discovery have for understanding autism?

TN: What we know from studies of genetics is that loss-of-function mutations in certain genes confer a high risk for autism. What we have learned from developmental biology is that many of these genes tend to be most highly expressed during the early stages of brain development, and in the cerebral cortex in particular. One of the things that the field of autism research is trying to determine is when and where and what are the processes that are most vulnerable to mutations in those genes, with the hope of identifying these points of convergence that could be targeted therapeutically.

So if you were an autism researcher and you were interested in understanding how a particular mutation impacts the development of excitatory and inhibitory neurons in the human brain, you would typically plan to derive two different types of progenitor cells [from pluripotent stem cells] and then study how their development is affected by the mutation. Our findings suggest a new framework for studying the consequences of these mutations. A mutation could affect the generation of both excitatory and inhibitory neurons by affecting even just one population of progenitor cells.

S: One theory suggests that autism results from an imbalance between excitation and inhibition in the brain. How does your discovery affect that hypothesis?

TN: There are many ways in which such an imbalance could occur. One possibility is that the early differentiation into excitatory and inhibitory neurons is somehow affected, and the way to test that hypothesis would be to compare the generation or differentiation of these interneurons or excitatory neurons in parallel. But our findings suggest that even just a mutation disrupting normal development of cerebral cortical progenitors could affect the ratio or differentiation of these excitatory or inhibitory neurons.

There are several studies that suggest that excitatory and inhibitory neuron generation is affected by autism mutations. When we try to explain these studies, especially those using models based on pluripotent stem cells, the assumption is that these phenotypes are a result of this patterning or organization of these stem cells into two pools: one that generates inhibitory neurons and one that generates excitatory neurons. Our finding provides an alternative interpretation.

S: Tell us a bit about the viral barcoding tool you developed. Could it be used in other kinds of autism research?

TN: We utilize viruses that are originally derived from the human immunodeficiency virus (HIV). These viruses have a high efficiency of transecting a human cell and integrating their genomic information into the DNA of individual cells, but they cannot replicate or cause any major pathology. We have engineered these viruses to deliver a molecular barcode of information, which we have predefined in the laboratory. Current technologies of high-throughput sequencing enable highly sensitive readouts of that molecular barcode information from single cells, along with the recovery of information about all the genes that these cells express. When applied to these neural stem cells, the DNA barcode integrates into the genomic DNA of a progenitor cell and is subsequently inherited by all the neurons generated by this progenitor cell. This powerful technology allows us to determine what types of neurons have been born from the same progenitor cell, and the technology can be scaled to discover thousands of these lineage relationships in a single experiment.

Our tool can be applied to essentially any experimental model, since it does not depend on transgenic mouse models or genetically modified cell lines. The barcoded virus can be applied to any experimental study to track cells over time. Moreover, it doesn’t have to be restricted to tracking cell lineages. It could be also applied to other biological problems. For example, the barcoding method could be applied to other types of viruses, such as monosynaptic rabies virus, which is often used to track synaptic connections.

S: Because the versatility you found doesn’t occur in mice, what does that say about using mouse models to study autism?

TN: I think that it is fair to say that if a particular autism mutation does have an impact on the local generation of inhibitory neurons in the cerebral cortex, you wouldn’t be able to detect it using mice as a model. The ramification of this findings is that one would have to identify alternative models to address that question.

Embedded in this finding is an opportunity to think about what organisms other than mice could serve as in vivo experimental models.

S: Is there anything else that really excites you about this discovery?

TN: When we look at the mouse, at the mouse cerebral cortex, the ratio of these excitatory and inhibitory neurons is about 5 to 1. When you look at humans and marmosets, which is another emerging animal model for human neuroscience, this ratio changes to about 2 to 1 for humans, and about 3 to 1 for marmosets. And so it really motivates you to think about what evolutionary changes between mice and humans may have caused this ratio to change so dramatically. One of the hypotheses was that perhaps the GABA-ergic interneurons could be locally generated by cortical generator cells. The evidence has gone back and forth over the years, but our study provides a strong argument that indeed this phenomenon may have been underappreciated.

S: What are you going to delve into next?

TN: I am very interested in identifying the mechanism underlying the generation of cortical interneurons by local cortical progenitor cells. The possibility that the switch between excitatory and inhibitory neuron generation could be affected by autism mutations is really exciting, and important to explore. More broadly, I am fascinated by neurodevelopmental differences between mice and humans. Identifying the experimental models that better recapitulate human neural developmental events represents a really important challenge. While there is a growing interest in using brain organoids, for example, to study these early neurodevelopmental processes, there are many important features of brain development and function that cannot be modeled in a dish.

Cite this article: https://doi.org/10.53053/FANB1055

The post Rethinking the origins of neurons: Q&A with Tomasz Nowakowski appeared first on Spectrum | Autism Research News.

It’s 2022 and By the Numbers is back. Last week, we released the Autism Drug Trial Tracker, an interactive tool to explore hundreds of clinical trials for autism and related conditions. All the code and data are open source, and we hope it proves useful to the autism research community. We’ll update the tool regularly, as new data become available.

Let us know what you think of the newsletter, or the drug trial tracker, at niko@spectrumnews.org. Thanks for reading.

Between 2018 and 2021, the number of board-certified behavioral analysts (BCBAs) — who provide the standard autism therapy applied behavior analysis — jumped from 27,320 to 45,103 in the United States, a 65 percent increase, according to a new study. But that rapid growth was uneven. Nearly half the counties in the U.S. still lack a single BCBA, and most of the growth is concentrated in large, coastal cities.

The study relied on data from the U.S. Department of Education and an online registry of certified behavioral analysts to determine the number of licensed providers in 3,318 counties and county equivalents, such as parishes and independent cities, across the U.S. Of those, just 266 added a BCBA during the study period.

The findings appeared in the Journal of Autism and Developmental Disorders earlier this month.

About 1.6 and 1.3 percent of children covered by public or private insurance, respectively, are diagnosed with autism by age 8. That’s according to a new study in JAMA Psychiatry that analyzed birth cohort data for more than 2 million publicly insured and more than 1.3 million privately insured children.

The researchers also stratified the data based on birth year, maternal age and race. More children born in recent years appeared to be diagnosed than those born earlier. And white publicly insured children in the study were twice as likely to be diagnosed with autism as Black, Asian or Hispanic publicly insured children.

Autistic people are 38 percent less likely to be proceeded against, 40 percent less likely to be charged and 44 percent less likely to be convicted following a police interaction than their non-autistic peers in the island nation of New Zealand. Autistic people are incarcerated at a slightly higher rate than non-autistic people, though.

The data include 1,197 people with autism and 147,879 without autism who had a police interaction when they were between 17 and 25 years old. The study, published in Autism in December, claims to be the first to examine pathways through a criminal justice system for a national sample of young adults with or without autism.

A prior study of 431 male prisoners in the U.S., by contrast, found that 4.4 percent of them had autism, which is double the prevalence in the general population. Spectrum has previously covered the challenges of being incarcerated and autistic.

Spectrum index:

8.1: The additional number of autism diagnoses per 1,000 children per quarter when screening for the condition using questionnaires and diagnostic evaluations. Spanish-speaking families saw the greatest benefit from this multi-pronged approach. The results, based on data from the Massachusetts Department of Public Health, were published in JAMA Pediatrics in January.

95: The percentage of children accurately screened as not having autism using a 10-item version of the Quantitative Checklist for Autism in Toddlers (Q-CHAT), according to a study in Molecular Autism in January. That specificity bests two revised versions of the Modified Checklist for Autism in Toddlers (M-CHAT), the predominant tool used to screen toddlers.

13: The percentage of autistic children who were referred for applied behavior analysis (ABA) but never received it, according to data from a single healthcare clinic in Southern California. The study also found that 66 percent of children who initiated ABA continued for 12 months, and less than half completed the recommended 24 months of therapy. The work was published in the Journal of Developmental and Behavioral Pediatrics in January.

Cite this article: https://doi.org/10.53053/ECIQ9635

The post By the Numbers: Unequal ABA access, autism incidence by insurance type, criminal charges counts appeared first on Spectrum | Autism Research News.

It’s 2022 and By the Numbers is back. Last week, we released the Autism Drug Trial Tracker, an interactive tool to explore hundreds of clinical trials for autism and related conditions. All the code and data are open source, and we hope it proves useful to the autism research community. We’ll update the tool regularly, as new data become available.

Let us know what you think of the newsletter, or the drug trial tracker, at niko@spectrumnews.org. Thanks for reading.

!function(){“use strict”;window.addEventListener(“message”,(function(e){if(void 0!==e.data[“datawrapper-height”]){var t=document.querySelectorAll(“iframe”);for(var a in e.data[“datawrapper-height”])for(var r=0;r<t.length;r++){if(t[r].contentWindow===e.source)t[r].style.height=e.data[“datawrapper-height”][a]+”px”}}}))}();

Between 2018 and 2021, the number of board-certified behavioral analysts (BCBAs) — who provide the standard autism therapy applied behavior analysis — jumped from 27,320 to 45,103 in the United States, a 65 percent increase, according to a new study. But that rapid growth was uneven. Nearly half the counties in the U.S. still lack a single BCBA, and most of the growth is concentrated in large, coastal cities.

The study relied on data from the U.S. Department of Education and an online registry of certified behavioral analysts to determine the number of licensed providers in 3,318 counties and county equivalents, such as parishes and independent cities, across the U.S. Of those, just 266 added a BCBA during the study period.

The findings appeared in the Journal of Autism and Developmental Disorders earlier this month.

!function(){“use strict”;window.addEventListener(“message”,(function(e){if(void 0!==e.data[“datawrapper-height”]){var t=document.querySelectorAll(“iframe”);for(var a in e.data[“datawrapper-height”])for(var r=0;r<t.length;r++){if(t[r].contentWindow===e.source)t[r].style.height=e.data[“datawrapper-height”][a]+”px”}}}))}();

About 1.6 and 1.3 percent of children covered by public or private insurance, respectively, are diagnosed with autism by age 8. That’s according to a new study in JAMA Psychiatry that analyzed birth cohort data for more than 2 million publicly insured and more than 1.3 million privately insured children.

The researchers also stratified the data based on birth year, maternal age and race. More children born in recent years appeared to be diagnosed than those born earlier. And white publicly insured children in the study were twice as likely to be diagnosed with autism as Black, Asian or Hispanic publicly insured children.

!function(){“use strict”;window.addEventListener(“message”,(function(e){if(void 0!==e.data[“datawrapper-height”]){var t=document.querySelectorAll(“iframe”);for(var a in e.data[“datawrapper-height”])for(var r=0;r<t.length;r++){if(t[r].contentWindow===e.source)t[r].style.height=e.data[“datawrapper-height”][a]+”px”}}}))}();

Autistic people are 38 percent less likely to be proceeded against, 40 percent less likely to be charged and 44 percent less likely to be convicted following a police interaction than their non-autistic peers in the island nation of New Zealand. Autistic people are incarcerated at a slightly higher rate than non-autistic people, though.

The data include 1,197 people with autism and 147,879 without autism who had a police interaction when they were between 17 and 25 years old. The study, published in Autism in December, claims to be the first to examine pathways through a criminal justice system for a national sample of young adults with or without autism.

A prior study of 431 male prisoners in the U.S., by contrast, found that 4.4 percent of them had autism, which is double the prevalence in the general population. Spectrum has previously covered the challenges of being incarcerated and autistic.

Spectrum index:

8.1: The additional number of autism diagnoses per 1,000 children per quarter when screening for the condition using questionnaires and diagnostic evaluations. Spanish-speaking families saw the greatest benefit from this multi-pronged approach. The results, based on data from the Massachusetts Department of Public Health, were published in JAMA Pediatrics in January.

95: The percentage of children accurately screened as not having autism using a 10-item version of the Quantitative Checklist for Autism in Toddlers (Q-CHAT), according to a study in Molecular Autism in January. That specificity bests two revised versions of the Modified Checklist for Autism in Toddlers (M-CHAT), the predominant tool used to screen toddlers.

13: The percentage of autistic children who were referred for applied behavior analysis (ABA) but never received it, according to data from a single healthcare clinic in Southern California. The study also found that 66 percent of children who initiated ABA continued for 12 months, and less than half completed the recommended 24 months of therapy. The work was published in the Journal of Developmental and Behavioral Pediatrics in January.

Cite this article: https://doi.org/10.53053/ECIQ9635

The post testing embed chart. appeared first on Spectrum | Autism Research News.

Black, Hispanic/Latino and Asian/Pacific Islander autistic people in the United States have higher odds of having co-occurring health conditions, such as diabetes, cardiovascular disease or hypertension, compared with white autistic people, according to a new study.

The same disparities exist in the general population and are likely linked to multiple factors, including a lack of access to healthcare, exposure to poorer air quality and systemic discrimination toward these racial and ethnic groups, says lead investigator Whitney Schott, research scientist at Drexel University in Philadelphia, Pennsylvania. Genetic differences may also play a role, the study notes.

Schott and her colleagues analyzed the prevalence of health conditions listed in insurance claims data for more than 155,000 autistic and 466,000 non-autistic adults in the U.S. who were covered by Medicaid — a government-funded healthcare program — between 2008 and 2012. They matched the autistic and non-autistic participants for age, sex, race and ethnicity, and controlled for differences in intellectual ability.

The prevalence of infections, cardiovascular disease and cancer was similar between autistic and non-autistic people overall, the researchers found. But people with autism had higher odds of having several different kinds of psychiatric conditions, including obsessive-compulsive disorder (OCD), attention deficit hyperactivity disorder and anxiety.

Black and Hispanic/Latino autistic adults had 20 to 40 percent higher odds of having schizophrenia and other psychoses compared with white autistic adults. Yet Black autistic people were 25 to 50 percent less likely to have OCD or anxiety.

Black and Hispanic/Latino people with autism were also significantly more likely to be diagnosed with hypertension, diabetes and obesity than were white people. Asian/Pacific Islander people with autism also showed higher odds of specific health conditions, including diabetes, Down syndrome and hypertension.

The study was published in Autism Research in December 2021.

The results could help policymakers devise new strategies to determine who most needs access to Medicaid and how resources should be allocated, the researchers say.

The study’s findings are not necessarily representative of the general population, because people who qualify for Medicaid must have disabilities or low income, or meet some other criteria. And many states lack data on race and ethnicity, which could have skewed the results.

To ease racial and ethnic disparities, public health interventions, such as Medicaid expansion, should use targeted outreach efforts and provide more healthcare services in autistic people’s homes or communities, the team suggests.

“Providing needed supports and outreach can help narrow the health gap among these historically more vulnerable groups,” Schott says.

The post Autism comorbidities reflect racial, ethnic disparities appeared first on Spectrum | Autism Research News.

Pregnant mice that mount an immune reaction have pups with autism-like traits and an increased susceptibility to gut inflammation, according to a new study.

The results may help to explain why many autistic people have gastrointestinal issues, says study investigator Eunha Kim, a postdoctoral researcher in Jun Huh’s lab at Harvard University.

Previous work has shown that prenatal exposure to a mother’s immune response — elicited by a viral mimic — induces autism-like traits in mice. And a severe infection or an overactive immune system during pregnancy increases the likelihood of having an autistic child, other studies have found.

But a different mechanism underlies the gut issues, Kim and her colleagues found. They stem from alterations in the mother’s gut microbiome — the mix of microbes that inhabit the stomach and intestines — to which the pups are exposed after birth. The mother’s atypical gut microbiome, in turn, primes the pups’ immune system to overreact to infections later on.

Studying this newly identified mechanism may help researchers better understand how maternal immune activation and autism are linked to other conditions, such as allergies, says John Lukens, associate professor of neuroscience at the University of Virginia in Charlottesville. Lukens was not involved in the study but wrote about the findings in a preview article.

“It could be some kind of evolutionary advantage that’s gone haywire,” he says.

Kim and her colleagues injected pregnant mice with either a mock virus or saline. As adults, the male offspring exposed to the mock virus had atypical social behaviors, akin to those seen in people with autism.

The team then infected the adult offspring with the bacterium Citrobacter rodentium, which can cause an inflammatory gut condition resembling colitis. Ten days after infection, the mock-virus-exposed animals of both sexes had shortened colons — a sign of colitis — and increased levels of the inflammatory immune molecule IL-17A.

When the mice born to mock-virus-treated mothers were instead reared by saline-injected mothers, they still had autism-like behaviors, but they no longer produced a rapid inflammatory response to a pathogen. The offspring of saline-treated mice that were raised by mock-virus-treated mothers, on the other hand, did — suggesting that the enhanced immune response is acquired after birth. The findings were published in Immunity 7 December.

One way that a mother influences her offspring’s immune system during typical development is through the gut microbiome. Mice, in particular, eat their cagemates’ feces, which alters the contents of their gut. In this way, changes to a mother mouse’s microbiome can disrupt how her pup’s immune system is established.

The mock-virus-treated mice, Kim and her colleagues found, have an atypical and less diverse gut microbiome than do their saline-injected counterparts. And germ-free mice that received a fecal transplant from mock-virus-treated mice went on to have their own pups with an enhanced immune response, further implicating the mothers’ microbiome.

Pups reared by mothers with this atypical, less diverse microbiome have altered helper T cells, which release IL-17A and other immune molecules to sound the alarm for other immune cells after exposure to a pathogen. The T cells in these pups, the study shows, have differences in the accessibility of their chromatin — the tightly coiled form of DNA — which causes them to produce an unusually high level of IL-17A, and thus inflammation, in response to an immune system challenge.

Injecting pregnant mice with a compound that blocks IL-17A before treating them with the mock virus prevented the pups they reared from having a heightened immune response to a later infection, the team found, confirming the immune molecule’s involvement.

Though the study doesn’t explain how autism arises in people, “it’s giving you information about the role of early-life microbes in immune reactivity,” says Jane Foster, professor of psychiatry and behavioral neurosciences at McMaster University in Hamilton, Canada, who was not involved in the study.

IL-17A often turns up in studies of atypical immune responses and autism, and previous work by Kim’s colleagues found that blocking IL-17A in pregnant mice that experience maternal immune activation prevents their pups from developing autism-like traits.

Similarly, “blocking IL-17A activity may be a potential therapeutic target” for preventing gastrointestinal issues in some children, Kim says. But because the molecule has many other functions, “this needs to be further carefully investigated,” she says.

A safer option, Lukens says, may be to try to normalize a mother’s gut microbiome with a specific diet or probiotics.

But it is unclear how the microbiome would need to change to achieve that goal. “The thing that’s missing here is they didn’t actually map those microbes” to pinpoint which ones are important, Foster says.

Kim and her colleagues plan to look into this next. They also plan to explore whether these findings hold up in children exposed to a maternal immune response, Kim says.

Cite this article: https://doi.org/10.53053/YNWN9651

The post Infection in pregnant mice ups risk of gut problems in pups appeared first on Spectrum | Autism Research News.

The U.S. Food and Drug Administration (FDA) has granted ‘breakthrough device’ designation to a hair-based test designed to aid autism diagnosis. The acknowledgment shifts the test into a fast lane through the agency’s regulatory review process.

The test, called StrandDx, analyzes the levels of chemicals in a strand of a child’s hair to capture a snapshot of her ‘exposome’ — some of her cumulative environmental exposures and how she regulates certain essential nutrients. The measures suggest how a person’s physiology responds to her environment, which can predict her chances of having autism, says Manish Arora, Edith J. Baerwald Professor and vice chairman of environmental medicine and public health at the Icahn School of Medicine at Mount Sinai in New York City and co-founder of New York-based Linus Biotechnology, which is developing the test.

Previous research from the test’s makers suggested that autistic people’s teeth contain atypical levels of some metals, and that that information can be used to predict autism diagnoses.

With further development, StrandDx could also help identify subtypes of autism and predict prognoses and who might benefit from which therapies, Arora says.

“We’re not just saying this is a diagnostic tool,” Arora says. “This is something we will help deliver therapy over time and chart the patient journey toward a healthier future.”

Other experts say it is difficult to evaluate the technology without knowing more about what markers it analyzes and how it compares with current gold-standard diagnostic methods. Arora says his team has submitted a paper for review that outlines how the analysis works, but he declined to share it with Spectrum, citing the journal’s embargo policies.

“The group can clearly measure a lot of things in biological samples,” says Gary Miller, professor of environmental health sciences at Columbia University, who is not involved with the company. “The question is, ‘How does that connect to autism?’”

Analyzing hair samples makes it possible to look at chemical exposures and how the body regulates them over time, Arora says, similar to how the rings of a tree can reveal its age and changing environment.

To use StrandDx, a clinician would request a kit to collect a hair sample from a child and return it to the company. The company would then provide the analysis to the clinician to use in conjunction with other information, such as behavioral observations and family history, Arora says. The technology is intended to help predict the likelihood that a child has autism from birth to 18 months of age and assist in diagnosis from 18 months to 21 years.

Being able to evaluate many different molecules together — rather than looking for a single marker in, say, a blood sample — is a strength of the test, says Joseph Braun, associate professor of epidemiology at Brown University in Providence, Rhode Island. (Braun sometimes collaborates with Arora but is not involved with StrandDx or the research behind it.) And if it can effectively predict autism at some point, that is helpful even if researchers don’t understand the mechanisms behind it.

“Developing something like this would really be useful,” Braun says. “If you could predict autism really well with the surface temperature of Venus on the day you were born, who cares why?”

But it is unclear how hair could provide information about exposures that occurred prenatally, when autism is thought to develop, Miller says. The first centimeter or so of hair growing from a follicle generally reflects only the past 30 days of someone’s exposures, though it’s feasible signatures extending beyond the hair’s lifespan could be detected with more development, he says.

Collecting multiple samples over time may help, but by then a person might be able to obtain a diagnosis using other measures.

“The question is, how many samples do you need to see that trajectory?” Miller says. “If you need six months of data, it may be clinically diagnosed by then.”

Arora and his team have data demonstrating that StrandDx can detect autism from infancy through adulthood, Arora says.

For the next step in the FDA review, Arora and his team plan to compare StrandDx’s results with clinician evaluations that use gold-standard measures — work for which they hope to recruit about 5,000 children, Arora says.

Data from this study should inform the FDA’s evaluation of the technology and provide crucial information about which markers StrandDx should focus on. Those results are crucial to evaluate how clinicians should view StrandDx, says Stephen Sheinkopf, executive director of the Thompson Center for Autism and Neurodevelopmental Disorders at the University of Missouri, who was not involved with the work.

“Before we get too excited about something like this, we need to know more about its sensitivity and specificity and just how it’s performing,” he says.

Developing predictive biomarkers such as StrandDx is particularly difficult given the “shifting diagnostic boundaries” of autism, Sheinkopf says. Different markers may emerge depending on who is considered for inclusion in a study, for example.

“The field is still grappling with how broadly we should define autism,” he says. “That creates a major challenge for developing tests like this.”

If the team can identify concrete markers of autism, and in particular autism subtypes, that would be beneficial for the field, Miller says.

“I think it’s a very exciting development,” he says. “But we just have to wait to see the data.”

Cite this article: https://doi.org/10.53053/OHGR9325

The post FDA cites hair-based autism diagnostic aid as ‘breakthrough’ appeared first on Spectrum | Autism Research News.

Hello, and welcome to the Community Newsletter! I’m your host, Chelsey B. Coombs, Spectrum’s engagement editor.

Twitter served up some practical tips this week about how to make magnetic resonance imaging (MRI) more comfortable for autistic people. Strategies in the literature could lead to new training materials for clinicians and scientists, a team of researchers wrote in a recent review.

https://t.co/snkyVSUp34

Our latest work on #autism-friendly #MRI, with gratitude to a great team, our reviewers, especially Prof @MikleSouth, all the key stakeholders, charities and @SCoRMembers for funding. Here is to learning and to hoping we can change #MRI practice.

— Christina Malamateniou (she/her) (@CMalamateniou) December 28, 2021

Noisy, narrow MRI machines can be especially challenging environments for autistic people, who may have sensory sensitivities, anxiety or communication challenges. Their discomfort can confound a study’s results, and sedation can cause side effects, especially in children.

To improve the experience, researchers and clinicians can send information about the MRI process ahead of time and use a person’s preferred communication style, the review notes. They can reduce wait times, provide a quiet waiting room with dimmable lights and offer autistic people weighted blankets, headphones, stress balls, movies or music during the scan. Simulated MRI experiences before the procedure can also help lower anxiety.

Mikle South, professor of psychiatry and behavioral sciences at Emory University and director of the Emory Autism Center in Atlanta, Georgia, peer-reviewed the paper before its publication and tweeted that the field should use these tips in the future.

It’s a great review and agree about doing things better going forward! Good work.

— Mikle South (@MikleSouth) December 30, 2021

Neil Woodhouse, a clinical manager for MRI at NHS Blackpool Teaching Hospitals in the United Kingdom, tweeted that he will use the recommendations in his practice.

Great review of considerations and adjustments for #MRI of #Autistic patients.
Will definitely inform our practice ⁦@BlackpoolHosp⁩ https://t.co/mKHTuhRZNc

— Neil Woodhouse (@RealNeil71) December 28, 2021

Mary Doherty, an anesthetist at Our Lady’s Hospital, Navan, in Ireland and founder of Autistic Doctors International, tweeted that the review shows how important it is to consult with autistic people during research.

A systematic review from a great project team looking at accessible MRI, which also shows the importance of involving autistic people in research@Autistic_Doc @GColleranMD https://t.co/JjiEnUXPh7

— Mary Doherty (@AutisticDoctor) December 28, 2021

Also this week, we are highlighting a tweet thread from Thomas Südhof, Nobel prize winner and professor of molecular and cellular physiology and of neurosurgery at Stanford University in California.

Check out our latest preprint! We ask a question that textbooks in various fields consider closed: does learning require long-term potentiation (LTP) of synapses? Read along for a surprise, insights into neural dynamics, and salience coding. https://t.co/qHl4317yfU

— Thomas Südhof Laboratory (@SudhofThomas) January 6, 2022

“Read along for a surprise,” Südhof wrote about a new preprint from his lab, which upends a popular idea about learning — namely, that it requires long-term potentiation of synapses.

Luke Rowe, a cognitive scientist and lecturer at Australian Catholic University in Victoria, and others described the work as mind-blowing.

This paper blew my mind. It challenges something I thought was a foundational principle of learning in the brain: that learning manifests, without much exception, in LTP of synapses… apparently not! Blocking LTP only partially impairs learning. Read for more details https://t.co/Ib0bg0S57Q

— Luke Rowe, Ph.D. (@LukeIRowe) January 9, 2022

“At last!” tweeted Huda Akil, professor of psychiatry and research professor of molecular neuroscience at the University of Michigan in Ann Arbor.

This is awesome! At last!
“Contrary to current conceptual frameworks, we found that hippocampal CA1-region LTP is not required for accurate representations of space in hippocampal neurons, but rather endows these neurons with reward- and novelty-coding properties.”???? https://t.co/Tzl8HpG77m

— Huda A (@Huda_Akil1) January 8, 2022

The work establishes an “interesting trend in the Südhof lab’s literature: rewriting the textbooks,” tweeted Matthew Kraushar, research group leader at the Max Planck Institute for Molecular Genetics in Berlin, Germany.

interesting trend in the Südhof lab’s literature: rewriting the textbooks on heavily studied molecules and mechanisms ????????

excellent reminder: do not be complacent – ideas are not settled, but always evolving!

first glutamate receptors:https://t.co/DXrFIcv9QU

now LTP! ???? https://t.co/QBEWkNZ82p

— Matthew L. Kraushar (@MatthewKraushar) January 7, 2022

Register for the next Spectrum webinar, featuring the co-chairs of the Lancet Commission: Tony Charman, chair of clinical child psychology at King’s College London in the U.K., and Catherine Lord, distinguished professor of psychiatry and education at the University of California, Los Angeles. They will speak about the commission’s recommendations and the use of the term ‘profound autism’ to refer to autistic people with intellectual disability, limited communication abilities or both.

That’s it for this week’s Community Newsletter! If you have any suggestions for interesting social posts you saw in the autism research sphere, send an email to news@spectrumnews.org.

The post Community Newsletter: Making MRIs more comfortable for autistic people, long-term potentiation and learning appeared first on Spectrum | Autism Research News.

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A new harmless virus can deliver genes to brain cells without infecting other tissues, according to early tests in mice and monkeys. The virus could minimize the risk of side effects from gene therapies under development for autism-related conditions, such as Angelman syndrome, Rett syndrome and fragile X syndrome.

Gene therapy typically involves replacing a faulty gene with a working copy, delivered into cells via a harmless adeno-associated virus (AAV). Some AAVs injected into the blood can cross the blood-brain barrier to replenish faulty genes in brain cells. Because these therapies require high doses, however, they run the risk of causing high levels of gene expression in unwanted tissues such as the liver, which can prompt harmful immune reactions.

To avoid widespread expression, researchers can use other AAVs that include neuron-specific regulatory elements, which act as genetic switches and activate the therapeutic gene only inside neurons. But these additions take up crucial space inside tiny AVV particles, where every nanometer matters.

To overcome these hurdles, Viviana Gradinaru, professor of neuroscience and biological engineering at the California Institute of Technology in Pasadena, and her colleagues used directed evolution to engineer viruses that target the brain and steer clear of other organs. The approach follows the same principles that breeders use to select for useful traits in livestock.

The team started with a library of AAV viruses that each carry a different version of the protein responsible for latching onto host cells. They injected the mutated viruses into the bloodstream of mice and tested the viruses’ ability to infect the brain and other tissues. They created a new library of the most brain-specific variants, and then repeated the tests in mice.

After two rounds of selection, they generated a variant with high specificity for neurons and low uptake in the liver in mice, and it performed similarly in marmosets, the team found. The results were published in Nature Neuroscience in December.

In evolutionary terms, two ‘generations’ is an incredibly small amount of time, Gradinaru says. She and her colleagues achieved their results so quickly by selecting for viruses that incorporated their genetic material into the genome.

The approach could be used to engineer variants with additional traits or specificity for other tissues, the researchers say. Work is underway in Gradinaru’s lab and others to engineer brain-specific variants that can avoid neutralizing antibodies, which accumulate throughout a person’s lifetime and may reduce the effectiveness of gene therapies. Gradinaru has founded Capsida Biotherapeutics, a biotech company in Thousand Oaks, California, to develop AAV-based therapies.

Cite this article: https://doi.org/10.53053/KPAM3598

The post Neuron-specific virus overcomes barriers to brain-related gene therapy appeared first on Spectrum | Autism Research News.

Kristin Sohl learned young how to access community resources designed to help families through lean times: She had her first child at 19 years old.

“I was a premed student with no income,” she says. “My husband had just finished college, was starting work on his master’s degree and was working full-time as a pharmacy technician. We had a total family income of about $19,000, and we needed help.”

Today she is a pediatrician who shares the knowledge she gained then with other families — primarily those with autistic children, who make up most of her practice.

Most pediatricians lack training in recognizing and treating autism, says Sohl, professor of clinical pediatrics at the University of Missouri in Columbia. To address that gap, in 2015 she founded ECHO Autism, a virtual learning network that connects physicians and other primary-care providers with autism specialists around the world. She is also a principal investigator for the Autism Care Network, a group of 20 centers across North America that provide healthcare to autistic people, collect and share data, and conduct research.

Sohl recently told Spectrum why pediatricians need to be well versed in autism, why a ‘sponsor’ is better than a ‘mentor,’ and how Pokémon Go helps her refresh.

Spectrum: How did you decide to become a pediatrician?

Kristin Sohl: When I was 7, I broke my arm and had to spend the night in a hospital. My roommate there had been in a car accident and had extensive burns over her whole body. Watching her resilience and joy, despite the hurt, really moved me. Since then, I’ve never veered from my passion to be a physician. Fast forward a decade or so, and I earned a scholarship to medical school while I was a senior in high school. I decided to be a pediatrician because I love how much kids teach us through their innocence.

S: What did you learn about autism in medical school?

KS: Honestly, I didn’t learn about autism in medical school. That’s one of the reasons I’m so passionate about engaging physicians and clinicians in learning more, so we can reduce the stigma associated with developmental disabilities and autism. Most pediatricians don’t know what autism looks like across its broad spectrum. When one of them says, “Nah, I don’t think that’s autism,” that child’s outcome will be totally impacted.

S: What does a typical day look like for you?

KS: My day starts with getting up at 6 a.m. and getting to it. I am usually out of the house at 7:10 to take my daughter Isabella to school, and then I go to Panera for some quiet time and iced tea. I go into my first meetings or clinic around 8:30. No day is the same. Some days I’m planning new programs for Missouri and working on budgets, whereas other days I’m launching international partnerships and recruiting families for studies. Or I’m strategizing our next training session to engage more people in the ECHO Autism movement or plotting how to improve population health for children in Missouri. A ton of my free time is spent brainstorming with colleagues and thinking about how we can do something to make a difference in gaps that we see every day.

S: Do you have a mentor?

KS: I have a couple of sponsors, as I think of them. Sanjeev Arora, a hepatologist at the University of New Mexico, founded Project ECHO to bring effective treatment for hepatitis C to patients in sparsely settled areas in New Mexico. Now there are ECHOs for pain, HIV, COVID-19, cancer. We were the first to apply it to autism.

He and Susan Hyman are the two who have cleared paths for me and been my cheerleaders and guides through many experiences. Susan is a developmental behavioral pediatrician at the University of Rochester in New York, the founding chair of the Autism Subcommittee of the American Academy of Pediatrics, the godmother of autism in the pediatric space.

The way I see it, a mentor might give you some advice here and there, but a sponsor will say “This would be good for you,” and they connect you. They see what you want to accomplish, and they help you make it happen.

S: What is your family like?

KS: My husband David and I have two kids: Alexander, who’s 22, and Isabella, 13. They’re my favorite people. David grounds me, Alexander is the kindest soul I know, and Isabella pushes me to be my fierce self and stay authentic every day.

And I love cats. I have three — Diego, Percy and Roni. They watch TV with me. Roni is technically my grandcat, but I claimed him when my son moved back home during the pandemic.

S: When and where are you most productive?

KS: I’m most productive in a busy airport or a crowded cafe. I love to be in the middle of a lot of action, with headphones on and no one really knowing who I am.

S: What do you listen to while you work?

KS: Music for sure — I love contemporary Christian rock, Billie Eilish and ’80s music. Podcasts are also great. I usually listen to “Dare to Lead” with Brené Brown, or another leadership podcast, on my way to work.

S: Are you a reader?

KS: Yes! I love to read really good psychological thrillers, but right now I’m reading two nonfiction books: Harvard Business Review’s “Time Management” and Patrick Lencioni’s “The Four Obsessions of an Extraordinary Executive.”

S: What do you do to relax?

KS: I love to binge-watch true crime and psychological thrillers on TV, such as “You,” for example, and play games such as Spades and Settlers of Catan. I also play Pokémon Go (a mobile virtual game) with my best friend, who’s also a pediatrician. I roped my husband into it, too. I love it. It keeps me busy while I’m walking and getting exercise. My brain is ordinarily so nonstop “on” that if I just take a random walk, very soon I will go home, because I can’t stop thinking of things I need to do. Pokémon Go allows me to just totally enjoy the world around me.

Cite this article: https://doi.org/10.53053/QHBE6894

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